Title

Author

Date of Award

3-4-2008

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Charles Greer

Abstract

The distribution of cell types and synapses is well characterized in the rodent olfactory bulb (OB), and from that plausible models of odor processing have been constructed. Individual olfactory sensory neurons (OSNs) express only 1 of ~1000 odorant receptors (ORs) and send their axons to specific synaptic targets in the OB glomerular neuropil. Each glomerulus is innervated exclusively by OSN axons expressing the same OR. The distribution of these glomeruli is conserved across animals, as is the numerical relationship between number of expressed ORs and number of glomeruli in the OB. Our objective is to extend such results to the level of the human OB to determine how its cellular and synaptic organization, and more specifically how the number and distribution of its glomeruli, compare to what has been elucidated in mice. As there are ~2,000 glomeruli for ~1,000 ORs in mice, we predicted ~700 glomeruli in humans based on the ~350 intact OR genes identified in the human through genomic studies. Using immunohistochemistry, the organization of cells and synapses in human OBs was evaluated and quantified. While the laminar structure of the OB is broadly conserved between species, in the human OB the laminar organization as well as additional structural features suggest a less rigorously organized OB than in rodents, perhaps suggesting that odor processing in the human OB may be less efficient than in mice. Of particular note, the total number of glomeruli in the human OB differs significantly from predicted and demonstrates a high degree of variability amongst specimens, thus far ranging from approximately 3000 - 9000/OB. These results indicate that the principles of OR-homotypic axon convergence developed from mouse studies may not be readily applicable to the human, and that central processing of odor signals in the human may differ from those characterized in the mouse.